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High affinity single-chain variable fragments are specific and versatile targeting motifs for extracellular vesicles

Longatti, A; Schindler, C; Collinson, A; Jenkinson, L; Matthews, C; Fitzpatrick, L; Blundy, M; ... Tigue, N; + view all (2018) High affinity single-chain variable fragments are specific and versatile targeting motifs for extracellular vesicles. Nanoscale , 10 (29) pp. 14234-14244. 10.1039/c8nr03970d. Green open access

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Abstract

Exosomes are extracellular vesicles that mediate cell-to-cell communication by transferring biological cargo, such as DNA, RNA and proteins. Through genetic engineering of exosome-producing cells or manipulation of purified exosomes, it is possible to load exosomes with therapeutic molecules and target them to specific cells via the display of targeting moieties on their surface. This provides an opportunity to exploit a naturally-occurring biological process for therapeutic purposes. In this study, we explored the potential of single chain variable fragments (scFv) as targeting domains to achieve delivery of exosomes to cells expressing a cognate antigen. We generated exosomes targeting the Her2 receptor and, by varying the affinity of the scFvs and the Her2 expression level on recipient cells, we determined that both a high-affinity anti-Her2-scFv (KD ≤ 1 nM) and cells expressing a high level (≥106 copies per cell) of Her2 were optimally required to enable selective uptake. We also demonstrate that targeting exosomes to cells via a specific cell surface receptor can alter their intracellular trafficking route, providing opportunities to influence the efficiency of delivery and fate of intracellular cargo. These experiments provide solid data to support the wider application of exosomes displaying antibody fragments as vehicles for the targeted delivery of therapeutic molecules.

Type: Article
Title: High affinity single-chain variable fragments are specific and versatile targeting motifs for extracellular vesicles
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1039/c8nr03970d
Publisher version: http://dx.doi.org/10.1039/c8nr03970d
Language: English
Additional information: This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence.(https://creativecommons.org/licenses/by-nc/3.0/)
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Computer Science
URI: https://discovery.ucl.ac.uk/id/eprint/10053172
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